Clinical Trial: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of GSK2881078 in Single and Repeat Doses

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized Double Blinded (Sponsor Unblind), Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Selective Androgen Receptor Modulator (SARM)

Brief Summary: This study is the first administration of GSK2881078 to humans. The intention of this study is to provide sufficient confidence in the safety of the molecule to inform progression to further repeat dose and proof of concept studies. This study will include approximately 52 subjects and consist of 2 parts. Part A will consist of two cohorts of 8 subjects to assess the safety, tolerability, and pharmacokinetic (PK) of ascending single oral doses of GSK2881078. Cohorts 1 and 2 will include healthy male subjects. Part B (Cohorts 3, 4 and 5) will include three cohorts of 12 healthy male subjects to examine the safety, tolerability, PK, and pharmacodynamic (PD) of repeated doses of GSK2881078 over 14 days. The total duration of the study including screening and follow-up, is not expected to exceed 70 days.

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Vital sign assessment following single doses as a measure of safety and tolerability [ Time Frame: Up to 61 days ]
    Vital signs include: systolic blood pressure, diastolic blood pressure and heart rate
  • Vital sign assessment following repeat doses as a measure of safety and tolerability [ Time Frame: Up to 56 days ]
    Vital signs include: systolic blood pressure, diastolic blood pressure and heart rate
  • Cardiac telemetry following single doses as a measure of safety and tolerability [ Time Frame: Up to 19 days ]
    Continuous cardiac telemetry will be performed for at least 12 hours post dose in each treatment period in Part A.
  • Cardiac telemetry following repeat doses as a measure of safety and tolerability [ Time Frame: 14 days ]
    Continuous cardiac telemetry will be performed for at least 8 hours post dose in Days 1, 4, 7, 10, and 14 in Part B
  • Electrocardiogram (ECG) assessment following single doses as a measure of safety and tolerability [ Time Frame: Up to 61 days ]
    12-lead ECGs will be obtained during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF intervals) at each timepoint
  • ECG assessment following repeat doses as a measure of safety and tolerability [ Time Frame: Up to 56 days ]
    12-lead ECGs

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Composite of PK parameters following single doses [ Time Frame: PK samples will be collected at pre-dose and 0.2, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose in each of the four dosing session ]
      PK parameters include: area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinite]), area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC[0-t]), maximum observed concentration (Cmax), time of occurrence of Cmax (tmax), terminal phase half-life (t1/2)
    • Composite of PK parameters following repeat doses [ Time Frame: Up to 17 days ]
      PK parameters include: AUC (0-infinite), area under the concentration-time curve over the dosing interval (AUC [0-tau]), AUC (0-t), Cmax, tmax, t1/2 and accumulation ratio


    Original Secondary Outcome: Same as current

    Information By: GlaxoSmithKline

    Dates:
    Date Received: January 23, 2014
    Date Started: January 20, 2014
    Date Completion:
    Last Updated: May 5, 2017
    Last Verified: May 2017